The present invention relates to a process for synthesizing 1-aza-5-halo-5-stannabicyclo[3.3.3]undecane, which can be used for making compounds such as carbapenems.
Many of the carbapenems are useful against gram positive microorganisms, especially methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and methicillin resistant coagulase negative Staphylococci (MRCNS). These antibacterials thus comprise an important contribution to therapy for treating infections caused by these difficult to control pathogens. There is an increasing need for agents effective against such pathogens (MRSA/MRCNS) which are at the same time relatively free from undesirable side effects.
Previously reported synthesis of 1-aza-5-chloro-5-stannabicyclo[3.3.3]undecane proceeded in low yields, used highly toxic or expensive reagents and were impractical for large scale synthesis. See Jurkschat, K., et al., J Organometallic Chemistry, 272, C13-C16 (1984); Jurkschat, K., et al., Z. Anorg Allg. Chem. 560, 110-118 (1983); Vedejs, E. et al., J Amer. Chem. Soc. 114, 6556-6558, (1992); Haight, A., University of Wisconsin-Madison, Thesis for PH.D., entitled Intramolecular Activation of Tin-Hydrogen and Tin-Carbon Bonds, 1-216 (1990) and Lautens, M, et al., Agnew Chem. Int. ed. Engl., 35, 1329-1330 (1996).
The invention disclosed herein provides a reliable process for economically synthesizing 1-aza-5-halo-5-stannabicyclo[3.3.3]undecane intermediates.